Related Experiment Video

Updated: Dec 29, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

24.9K

Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss

Xijuan Liu1, Jeremy M Simon2, Haibiao Xie3

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

Molecular Cell
|February 6, 2020
PubMed

Insights

The von Hippel-Lindau (VHL) tumor suppressor pathway regulates SFMBT1 protein levels. Targeting the pVHL-SFMBT1-SPHK1 axis offers a new therapeutic strategy for clear cell renal cell carcinoma (ccRCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The von Hippel-Lindau (VHL) protein is a crucial tumor suppressor in clear cell renal cell carcinomas (ccRCCs).
  • Identifying therapeutic targets beyond HIF2α in VHL-deficient ccRCC is essential.
  • The role of SFMBT1 in cancer, particularly ccRCC, is not well understood.

Purpose of the Study:

  • To identify novel VHL target genes involved in ccRCC pathogenesis.
  • To investigate the function of SFMBT1 in ccRCC.
  • To elucidate the molecular mechanism linking VHL loss, SFMBT1, and ccRCC progression.

Main Methods:

  • Genome-wide screening to identify VHL target genes.
  • Western blotting to assess SFMBT1 protein levels in ccRCC patients.
  • In vitro and in vivo experiments to evaluate the effect of SFMBT1 depletion on ccRCC cells.
  • ChIP-seq, RNA-seq, and patient prognosis analyses to identify SFMBT1 target genes.

Main Results:

  • SFMBT1 was identified as a novel pVHL target gene.
  • Elevated SFMBT1 protein levels were observed in ccRCC patients with VHL loss-of-function mutations.
  • SFMBT1 hydroxylation by EglN1 mediated its degradation via pVHL.
  • SFMBT1 depletion inhibited ccRCC cell proliferation and tumor growth.
  • SPHK1 was identified as a key SFMBT1 target gene contributing to its oncogenic phenotype.

Conclusions:

  • The pVHL-SFMBT1-SPHK1 signaling axis plays a significant role in ccRCC development.
  • SFMBT1 acts as an oncogene in ccRCC by regulating SPHK1.
  • Targeting the pVHL-SFMBT1-SPHK1 pathway represents a promising therapeutic strategy for ccRCC.
Keywords:
SFMBT1SPHK1ccRCCpVHL

More Related Videos

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens09:33

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

Published on: August 25, 2023

1.5K
Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR10:34

Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR

Published on: February 1, 2013

14.6K

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.4K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.0K